Role of energy states and CART signalling in fear and extinction learning in rats

Abstract

The body is a complex machine that consists of several subsystems working together to stay alive and reproduce. These subsystems and the resulting behaviours are regulated by the brain to best negotiate the changing environment. Survival circuits, as these circuits are called, involve the regulation of defence, feeding, reproductive behaviour, homeostasis etc. Under conditions of stress, such as starvation, the brain must regulate the use of its limited resources and decide which survival circuits should be prioritised. Fear and extinction memory is an interesting process to study the effect of energy states on survival circuits. It involves interactions between fear and memory circuits and their regulation under different energy states. The neural circuitry underlying fear and extinction memories is well studied, and there is evidence that energy states do influence these memories. But how the energy state is able to influence these memories is not known. One possibility is via energy state responsive neuropeptides. One such neuropeptide, CART, is upregulated in the brain under satiety conditions and is involved in both fear and memory, suggesting its possible involvement in fear and extinction memory. To investigate whether energy levels have an effect on fear and extinction memory, adult Sprague Dawley rats were subjected to fear training under fed and starved conditions and then to extinction training. Extinction learning was found to be higher in animals that had been starved before fear conditioning. To investigate the role of CART neuropeptide in the same, injections were given in the CeA of CART Ab (in fed animals) or aCSF (in fed and starved animals) at two points of the extinction protocol, one set before the fear conditioning and the other set before extinction training. No significant difference could be found in either the fear or extinction memory in these experiments. However, the sample size is not sufficient and further tests need to be done in order to ascertain the involvement of CART in fear and extinction memory. This study therefore concludes that starvation stress enhances extinction learning. However, CART neuropeptide signalling may not be involved in this cross-talk between survival circuits. A key observation is that starvation stress at the time of fear memory acquisition influences extinction learning later. This suggests that the memory engram varies depending on the energy state of the animal.